Mental retardation and abnormal central nervous system (CNS) development are among the most devastating consequences of the fetal alcohol syndrome in humans. This research will determine the effect of ethanol exposure during days 1-21 of gestation on the developing neurons of the rat hippocampal formation. Muscarinic cholinergic neurons in the medial septal nucleus and nucleus of the diagonal band synapse on pyramidal cells and dentate gyrus cells. Stimlation of these muscarinic cholinergic receptors causes increases in cyclic GMP, a seoond messenger involved in synaptic transmission. Gestation in the rat is equivalent to the first and second trimesters in humans. We have already shown that rats exposed to ethanol from postnatal days 4 to 10 (equivalent to the third trimester in humans) experience a permanent derangement of hippocampal biochemistry, manifested in an increase in the cGHP response and larger dissociation constants and greater number of hippocampal muscarinic cholinergic receptors (see see appendix). (1) The proposed research will help determine the effect of ethanol administration during days 1-21 of gestation (first and second trimester equivalents) in the rat on the muscarinic cholinergic receptors and cyclic GMP responsiveness of the rat hippocampal formation at 90 days of postnatal age. This research will be compared with our previous results to determine which pattern of exposure results in greater damage to the rat hippocampal formation. (2) The pyramidal cells of the hippocampus are born during days 14-20 of gestation; the granule cells of the dentate gyrus are born postnatally. In some 90 day-old ethanol-exposed and both types of control rats, the hippocampus proper (pyramidal cells) will be separated from the dentate gyrus (granule cells). The hippocampus and dentate gyrus will be analyzed for muscarinic cholinergic receptors. Studying the effects of ethanol on these two different populations of cells will allow the determination of whether ethanol exposure during the period of neuronal development results in greater damage than that experienced by a group of cells in the same brain formation in the same rats which are born after the period of ethanol exposure.